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Structure of 113020-21-6

Chemical Structure| 113020-21-6

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Product Details of [ 113020-21-6 ]

CAS No. :113020-21-6
Formula : C6H8O4
M.W : 144.13
SMILES Code : COC(=O)C1(CC1)C(O)=O
MDL No. :MFCD06800496
InChI Key :IZYOHLOUZVEIOS-UHFFFAOYSA-N
Pubchem ID :13861823

Safety of [ 113020-21-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P270-P264-P271-P280-P312-P302+P352-P304+P340-P305+P351+P338-P330-P362+P364-P403+P233-P501

Computational Chemistry of [ 113020-21-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 31.64
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

63.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.22
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.16
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.04
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.15
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.31

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.64
Solubility 33.3 mg/ml ; 0.231 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.05
Solubility 12.8 mg/ml ; 0.0885 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.12
Solubility 108.0 mg/ml ; 0.75 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.07 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.52

Application In Synthesis of [ 113020-21-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 113020-21-6 ]

[ 113020-21-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 6914-71-2 ]
  • [ 113020-21-6 ]
YieldReaction ConditionsOperation in experiment
71% Synthesis of Cyclopropane-1,1-dicarboxylic acid methyl ester KOH (42 mg, 0.75 mmol) was added to a solution cyclopropane-1,1-dicarboxylic acid dimethyl ester (100 mg, 0.63 mmol) in methanol. The resulting mixture was stirred for 4 hours at ambient temperature then concentrated. The residue was diluted with water, acidified with conc. HCl and the product was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford 65 mg (71%) of cyclopropane-1,1-dicarboxylic acid methyl ester.
60% Preparation 201 -Methoxycarbon lcyclopropanecarboxylic acidDimethyl cyclopropane- 1, 1-dicarboxylate (26.08 mL, 189.87 mmol) is dissolved in methanol (319 mL) and the solution is cooled to 0 C. I NaOH (190 mL, 190 mmol, 1 eq) in water is added dropwise. The resulting mixture is stirred at RT overnight. The solution is concentrated under reduced pressure to remove the methanol and the resulting aqueous solution is washed with dichloromethane (3 x 50 mL) and acidified with 1 N HC1 (pH = 2-3). The solution is then extracted with ethyl acetate (5 x 100 mL) and dichloromethane (3 x 50 mL). The combined organic portions are dried over MgS04, filtered, and concentrated to afford the title compound (16.4 g, 60%). ¾ NMR(400 MHz, CDC13); delta 1.9-1.7 (m, 4H), 3.78 (s, 3H).
1,1-Cyclopropanedicarboxylic acid dimethyl ester (25 g) was dissolved in methanol (250 mL). The solution was cooled under ice cooling, and 1N aqueous sodium hydroxide (158 mL) was added dropwise thereto. The thus-obtained mixture was brought back to room temperature, and was stirred overnight. Methanol was distilled away, and the residue was washed with chloroform. The aqueous layer was cooled under ice cooling, and concentrated aqueous HCl was added thereto, to thereby adjust to pH 2. The resultant mixture was extracted with ethyl acetate, and the extract was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, to thereby give the title compound (16.8 g).1H-NMR(CDCl3) delta:1.76-1.80(2H, m), 1.82-1.88(2H, m), 3.79(3H, s), 12.73(1H, br).
With sodium hydroxide; In methanol; REFERENTIAL EXAMPLE 161 1-(Methoxycarbonyl)cyclopropanecarboxylic acid: Dimethyl 1,1-cyclopropanecarboxylate (25 g) was dissloved in methanol (250 ml), and the solution was cooled with ice. A 1N aqueous solution of sodium hydroxide (158 ml) was then added dropwise, and the resultant mixture was warmed to room temperature and stirred overnight. After methanol was distilled off, the residue was washed with chloroform, and a water layer was cooled with ice, adjusted to pH 2 with concentrated hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (16.8 g). 1H-NMR (CDCl3) delta: 1.76-1.80(2H,m), 1.82-1.88(2H,m), 3.79(3H,s), 12.73(1H,br).
Method C; <strong>[6914-71-2]Dimethyl 1,1-cyclopropanedicarboxylate</strong> (5 ml) was mixed with NaOH (1.4 g) in MeOH (40 ml)/water (4 ml). The reaction mixture was stirred at RT overnight and the solvent was evaporated. To the residue was added ether (50 ml), water (50 ml) and extracted once. The aqueous layer was acidified with 6N HCl and extracted three times with ether, the combined organic layer was washed with brine, dried and evaporated to give 1-(methoxycarbonyl)cyclopropanecarboxylic acid (4 g).
With sodium hydroxide; In methanol; water; at 0 - 20℃; [Referential Example 161] 1-(Methoxycarbonyl)cyclopropanecarboxylic acid: dimethyl 1,1-cyclopropanecarboxylate (25 g) was dissloved in methanol (250 ml), and the solution was cooled with ice.. A 1N aqueous solution of sodium hydroxide (158 ml) was then added dropwise, and the resultant mixture was warmed to room temperature and stirred overnight.. After methanol was distilled off, the residue was washed with chloroform, and a water layer was cooled with ice, adjusted to PH 2 with concentrated hydrochloric acid and extracted with ethyl acetate.. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (16.8 g).1H-NMR (CDCl3) delta: 1.76-1.80(2H,m), 1.82-1.88(2H,m), 3.79(3H,s), 12.73(1H,br).
<strong>[6914-71-2]Dimethyl 1,1-cyclopropanedicarboxylate</strong> (5 ml) was mixed with NaOH (1.4 g) in MeOH (40 ml)/water (4 ml). The reaction mixture was stirred at RT overnight and the solvent was evaporated. To the residue was added ether (50 ml), water (50 ml) and extracted once. The aqueous layer was acidified with 6N HCl and extracted three times with ether, the combined organic layer was washed with brine, dried and evaporated to give 1-(methoxycarbonyl)cyclopropanecarboxylic acid (4 g).
1.58 g With water; sodium hydroxide; In methanol; at 20℃; for 23h; (1) To a solution of dimethyl 1,1-cyclohexanedicarboxylate (2.08 g) in methanol (15 mL) was added a 1Naqueous sodium hydroxide solution (13.2 mL), and the mixture was stirred at room temperature for 23 hours. Themethanol was distilled off under reduced pressure, and the residue was washed with n-hexane. To an aqueous layerwas added 1N hydrochloric acid (10 mL), and the mixture was extracted with chloroform. The extract was washed withsaturated brine, and dried over anhydrous magnesium sulfate. After drying, concentration under reduced pressureprovided Compound 2 (1.58 g) as a colorless oil.
With water; lithium hydroxide; In methanol; at 20℃; for 1h; Dimethyl cyclopropane dicarboxylate (10.12 g, 63.99 mmol) was dissolved in 100 mL (1:1 V:V) CH3OH/H2O and stirred at room temperature. Lithium hydroxide (2.68 g, 63.99 mmol) dissolved in 20 ml H2O was slowly added to the above solution for three times at room temperature, and then the mixture was allowed to react for 1 h with stirring. After the reaction was completed, the resultant was adjusted to pH3 with dilute hydrochloric acid, extracted with DCM, and dried over anhydrous sodium sulfate. The product without purification was to be used in the next step.
With water; lithium hydroxide; In methanol; at 20℃; for 1h; A solution of dimethyl cyclopropane-1,1-dicarboxylate (10.12 g,63.99 mmol) in MeOH/H2O (100 mL, 1:1 V:V), stirring in room temperature,was treated dropwise with a solution of lithium hydroxide(2.68 g, 63.99 mmol) in 20 mL H2O. Stir for one hour after dropwise.Then adjust pH to 3 with dilute hydrochloric acid, extract with dichloromethane(50 mL) for three times, without purification go on nextstep.

  • 2
  • [ 6914-71-2 ]
  • [ 598-10-7 ]
  • [ 113020-21-6 ]
  • 3
  • [ 113020-21-6 ]
  • [ 849217-60-3 ]
 

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